CN102234675A - Fermentation medium and fermentation method of producing A40926 with Nonomuraea.sp by fermentation - Google Patents
Fermentation medium and fermentation method of producing A40926 with Nonomuraea.sp by fermentation Download PDFInfo
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Abstract
The invention provides a fermentation medium and a corresponding fermentation method in favor of efficiently producing an antibiotic A40926 with Nonomuraea.sp by fermentation. The fermentation medium comprises a carbon source and a nitrogen source, wherein, the carbon source is an organic carbon source with the content of 5-180g/L, the nitrogen source is an organic nitrogen source with the content of 2-210g/L, and the contents are measured as the total volume of the medium. By optimizing the components and ratio of carbon and nitrogen source of the fermentation medium, the cultural temperature, PH value and other fermentation parameters are optimized, so that the output of the A40926 is greatly improved. According to the method provided by the invention, the fermentation unit of the A40926 is greatly improved, so that the method is suitable for large-scale production of the A40926.
Description
Technical field
The invention belongs to the industrial microbial technology field, particularly a kind of new Ye Ye village actinomycete fermentation is produced fermention medium and the corresponding fermentation process of microbiotic A40926.
Background technology
1984, scientist found microbiotic A40926 during from the Madura of soil (Actinomadura) strain bacterium in culture of isolated.And (American Tissue Culture Collection ATCC), numbers ATCC39727 on June 8th, 1984 bacterial strain to be preserved in U.S. tissue culture preservation center.This strain is considered to belong to streptomyces at first, after after further study, particularly pair cell wall synthetic research in 2003, produces bacterium with it and ranges Ye Ye village actinomyces (Nonomuraea.sp).A40926 belongs to the vancomycin microbiotic, has the ability in conjunction with acyl group-D-propylamine acyl group-D-L-Ala.Gram-positive microorganism and neisseria gonorrhoeae (Neisseria gonorrhoeae) are had better anti-bacterial effect, and have the long transformation period.
Dalbavancin is to be the semi-synthetic glycopeptide antibiotics of precursor with A40926.Dalbavancin is by the development research of Vicuron company at first, is in the III clinical trial phase at present.Dalbavancin has the excellent antibiotic activity to gram-positive microorganism, and its mechanism of action is identical with teicoplanin with vancomycin, is mainly used in complicacy skin, soft tissue infection that treatment is caused by gram-positive microorganism.But biological activity that it is stronger and longer transformation period make it have more tempting DEVELOPMENT PROSPECT.Along with the continuous appearance of resistant organism, and the microbiotic with good resistance MRSA and VRE effect is developed slowly.Therefore, the appearance of dalbavancin has brought new hope and breakthrough for the clinical treatment resistant organism, and also attracting attention of insider extremely of the microorganism fermentation process of its precursor A40926.At present, A40926 is mainly produced by fermentation by gondola VicuronPharmaceuticals drugmaker, but the fermentating formula of its report only is some simple minimal mediums, and culture temperature is 28 ℃, incubation time 160h.Because the nutritive ingredient of its fermention medium kind only is some simple inorganic salt, the thalline vigor is relatively poor, and fermentation unit is lower, and the highest fermentation unit of its report is 128mg/L, and new zymotechnique both domestic and external does not see that report is arranged at present.
Summary of the invention
Therefore, the technical problem to be solved in the present invention is exactly to produce the low deficiency of microbiotic A40926 fermentation unit at the existing Ye Ye of utilization village actinomycete fermentation, a kind of new fermention medium and the corresponding fermentation process that are used for Ye Ye village actinomycete fermentation production microbiotic A40926 are provided, it can improve the fermentation unit of A40926 greatly, enhances productivity.
The present invention solves the problems of the technologies described above one of technical scheme of being adopted: the fermention medium of a kind of Ye Ye of being used for village actinomycetes (Nonomuraea.sp) fermentative production microbiotic A40926, comprise carbon source and nitrogenous source, wherein, described carbon source is an organic carbon source, content is 5-180g/L, described nitrogenous source is an organic nitrogen source, and content is 2-210g/L, and described content is by the cumulative volume of substratum.
In fermention medium of the present invention, described organic carbon source comprises various organic carbon sources commonly used in the substratum, preferable for being selected from glucose, maltodextrin, W-Gum and the Zulkovsky starch one or more, glucose and be selected from least a mixture in maltodextrin, W-Gum and the Zulkovsky starch more preferably.The consumption 5-180g/L of organic carbon source, preferred 15-100g/L.Wherein the more excellent scope of glucose is 5-20g/L, and the more excellent scope of maltodextrin is 10-80g/L, and the more excellent scope of W-Gum is 10-60g/L, and the more excellent scope of Zulkovsky starch is 5-20g/L.
In fermention medium of the present invention, described organic nitrogen source comprises in the substratum various organic nitrogen sources commonly used, and is preferable for being selected from soybean cake powder, cottonseed meal, peptone and the yeast extract (powder) one or more.What described soybean cake powder was preferable can be selected from hot moulding soybean cake powder and/or cold press soybean cake powder.Described peptone is one or more in soy peptone, Tryptones and the meat peptone preferably.Described yeast extract (powder) be adopt the fresh yeast emulsion through self-dissolving, enzymolysis, separation, refining a kind of solubility paste or the powdery natural product that forms of technology such as concentrate.Described organic nitrogen source more preferably is selected from least a in soybean cake powder, cottonseed meal and the peptone and is selected from yeast and soaks at least a mixture in powder and the yeast extract.The consumption of organic nitrogen source is 2-210g/L, preferred 30-50g/L.Wherein the more excellent scope of hot moulding soybean cake powder is 5-40g/L, the more excellent scope of cold press soybean cake powder is 5-40g/L, the more excellent scope of cottonseed meal is 5-30g/L, the more excellent scope of soy peptone is 2-20g/L, the more excellent scope of Tryptones is 2-20g/L, the more excellent scope of meat peptone is 2-20g/L, and it is 5-100g/L that yeast soaks the more excellent scope of powder, and the more excellent scope of yeast extract is 5-100g/L.
In the fermention medium of the present invention, as the actinomycetic fermention medium in Ye Ye village of routine, the preferable amino acid that also further comprises.In the preferred Xie Ansuan of described amino acid, leucine and the Isoleucine one or more, best is Xie Ansuan.Amino acid whose consumption is 0.5-3.0g/L, and more excellent scope is 1.0-2.5g/L.
In fermention medium of the present invention, the preferable metal ion that also further comprises.In described metal ion preferably copper ion, magnesium ion and the ferrous ion one or more.The consumption of metal ion is 0.05ppm-12.0ppm, and more excellent scope is 0.5-10.0ppm.
In the fermention medium of the present invention, as the actinomycetic fermention medium in Ye Ye village of routine, the preferable mineral substance that also further contains.Described mineral substance is generally as osmotic pressure regulator, and its consumption is 1.0-5.0g/L preferably.Described mineral salt can be employed various mineral salts, preferably NaCl in the conventional fermention medium.
Fermention medium of the present invention is as the fermention medium of the antibiosis streptomycete of routine, and preferable can also contain defoamer.The consumption of defoamer is a conventional amount used.
A preferred embodiment of the present invention is that fermention medium of the present invention comprises:
5-20g/L glucose;
At least a in 5-80g/L maltodextrin, W-Gum and the Zulkovsky starch;
At least a in 2-40g/L soybean cake powder, cottonseed meal and the peptone;
At least a in 5-100g/L yeast extract and the yeast extract powder; With
0.5-3.0g/L Xie Ansuan.
Another preferred embodiment of the present invention is that fermention medium of the present invention comprises: glucose 5-20g/L, dextrin 10-80g/L, W-Gum 10-60g/L, cold press soybean cake powder 5-40g/L, cottonseed meal 5-30g/L, soy peptone 2-20g/L, meat peptone 2-20g/L, yeast soak powder 5-100g/L, Xie Ansuan 0.5-3.0g/L, NaCl 1.0-5.0g/L and CuSO
40.5-10.0ppm.
The pH value of fermention medium of the present invention is pH5.0-8.5, more preferably pH5.5-8.0 preferably.
The present invention solves the problems of the technologies described above two of the technical scheme that adopted: the fermentation method for producing of a kind of microbiotic A40926 comprises step:
(a) seed liquor of Ye Ye village actinomycetes (Nonomuraea.sp) is inoculated in carries out liquid fermentation and culture in the fermention medium, described fermention medium is aforesaid each fermention medium;
(b) from fermented liquid, isolate microbiotic A40926.
In step (a), the actinomycetic seed liquor in described Ye Ye village method is routinely cultivated Ye Ye village actinomycetes and is obtained in seed culture medium.Described seed culture medium can be the actinomycetic seed culture medium in existing Ye Ye village, preferable ISP2 substratum and the M707 substratum of being selected from.Preferably 25-32 ℃ of the temperature of seed culture.
Among the present invention, described Ye Ye village actinomycetes can be existing various antibiosis streptomycete bacterial strain, preferably Ye Ye village actinomycetes ATCC39727.
In step (a), the temperature of described fermentation culture is 20-40 ℃, and more excellent is 25-37 ℃; Preferred pH is 5.0-8.5, and more excellent scope is 5.5-8.0.
In step (b), the method for isolating microbiotic A40926 from fermented liquid can be conventional method, generally is that fermented liquid is adjusted to alkalescence, and centrifuging and taking supernatant behind 50 ℃ of incubations obtains microbiotic A40926 from supernatant.
Among the present invention, but above-mentioned optimum condition arbitrary combination on the basis that meets this area general knowledge promptly gets the preferred embodiments of the invention.
Raw material that the present invention is used or reagent except that specifying, all commercially available getting.
Than prior art, beneficial effect of the present invention is as follows: the fermention medium and the corresponding fermentation process that the invention provides the efficient fermentative production microbiotic of a kind of Ye Ye of helping village actinomycetes A40926.By the carbon nitrogen source composition and the proportioning of preferred fermention medium, optimize fermentation parameters such as culture temperature, pH, thereby improve the output of A40926 greatly.The fermentation method for producing of A40926 provided by the invention has significantly improved the fermentation unit of A40926, is applicable to the large-scale production of A40926.
Embodiment
Further specify the present invention with embodiment below, but the present invention is not limited.The experimental technique of unreceipted actual conditions in the following example, usually according to normal condition, or the condition of advising according to manufacturer.
Embodiment 1
Get strain Ye Ye village actinomycetes (Nonomuraea.sp) ATCC39727 and line the seed slant medium, be inoculated in the shake-flask seed substratum behind 30 ℃ of cultivation 7d, liquid amount is 20ml/250ml, and in 30 ℃, the rotary shaking table of 200rpm is cultivated 72h.Seed liquor is inoculated in the 250ml fermentation shake flask that liquid amount is 20ml with 10% (v/v) inoculum size ferments 30 ℃ of leavening temperatures, fermentation period 5d.After the fermentation ends fermented liquid is transferred pH to 12.0 with NaOH, centrifuging and taking supernatant behind 50 ℃ of incubation 1h, HPLC measures, and A40926 output reaches 366mg/L.
Wherein used slant medium is formed: ISP2 substratum, component are glucose 4.0g/L, and yeast soaks powder 4.0g/L, and Fructus Hordei Germinatus soaks powder 10.0g/L, agar powder 20g/L, pH7.3.
Used seed culture medium is formed: ISP2 substratum, component are glucose 4.0g/L, and yeast soaks powder 4.0g/L, and Fructus Hordei Germinatus soaks powder 10.0g/L, pH7.3.
The composition of fermention medium: glucose 5.0g/L, dextrin 30.0g/L, W-Gum 60.0g/L, soy peptone 5.0g/L, meat peptone 10.0g/L, yeast soak powder 5.0g/L, cold press soybean cake powder 10.0g/L, cottonseed meal 5.0g/L, Xie Ansuan 1.0g/L, NaCl 2.0g/L, CuSO
40.75ppm, pH8.0.
Embodiment 2
Fermention medium is formed: glucose 10.0g/L, dextrin 5.0g/L, yeast soak powder 10.0g/L, hot moulding soybean cake powder 20.0g/L, NaCl 2.0g/L, pH to 8.0.
Be inoculated in the fermention medium with 10% (v/v) inoculum size by 1 seed that makes among the embodiment, 30 ℃ of leavening temperatures, fermentation period 7d, other conditions are with embodiment 1.A40926 output reaches 98mg/L.
Embodiment 3
Fermention medium is formed: glucose 10.0g/L, dextrin 5.0g/L, yeast soak powder 10.0g/L, hot moulding soybean cake powder 20.0g/L, Xie Ansuan 1.0g/L, NaCl 2.0g/L, pH to 8.0.
Be inoculated in the fermention medium with 10% (v/v) inoculum size by 1 seed that makes among the embodiment, 30 ℃ of leavening temperatures, fermentation period 7d, other conditions are with embodiment 1.The output of A40926 reaches 180mg/L.
Embodiment 4
Fermention medium is formed: glucose 10.0g/L, dextrin 50.0g/L, yeast soak powder 10.0g/L, hot moulding soybean cake powder 20.0g/L, Xie Ansuan 1.0g/L, NaCl 2.0g/L, pH to 8.0.
Be inoculated in the fermention medium with 10% (v/v) inoculum size by 1 seed that makes among the embodiment, 30 ℃ of leavening temperatures, fermentation period 7d, other conditions are with embodiment 1.The output of A40926 reaches 175mg/L.
Embodiment 5
Fermention medium is formed: glucose 10.0g/L, and dextrin 30.0g/L, Zulkovsky starch 10.0g/L, yeast soak powder 10.0g/L, hot moulding soybean cake powder 20.0g/L, Xie Ansuan 1.0g/L, NaCl 2.0g/L, pH to 8.0.
Be inoculated in the fermention medium with 10% (v/v) inoculum size by 1 seed that makes among the embodiment, 30 ℃ of leavening temperatures, fermentation period 7d, other conditions are with embodiment 1.The output of A40926 reaches 210mg/L.
Embodiment 6
Fermention medium is formed: glucose 5.0g/L, and dextrin 30.0g/L, W-Gum 60.0g/L, soy peptone 5.0g/L, yeast soak powder 10.0g/L, hot moulding soybean cake powder 20.0g/L, Xie Ansuan 1.0g/L, NaCl 2.0g/L, pH to 8.0.
Be inoculated in the fermention medium with 10% (v/v) inoculum size by 1 seed that makes among the embodiment, 30 ℃ of leavening temperatures, fermentation period 7d, other conditions are with embodiment 1.The output of A40926 reaches 214mg/L.
Embodiment 7
Fermention medium is formed: glucose 5.0g/L, and dextrin 30.0g/L, W-Gum 60.0g/L, yeast soak powder 10.0g/L, cold press soybean cake powder 20.0g/L, soya peptone 5.0g/L, Xie Ansuan 1.0g/L, NaCl 2.0g/L, pH to 8.0.
Be inoculated in the fermention medium with 10% (v/v) inoculum size by 1 seed that makes among the embodiment, 30 ℃ of leavening temperatures, fermentation period 7d, other conditions are with embodiment 1.The output of A40926 reaches 226mg/L.
Embodiment 8
Fermention medium is formed: glucose 5.0g/L, dextrin 30.0g/L, W-Gum 60.0g/L, yeast extract 10.0g/L, cold press soybean cake powder 20.0g/L, Xie Ansuan 1.0g/L, NaCl 2.0g/L, pH to 8.0.
Be inoculated in the fermention medium with 10% (v/v) inoculum size by 1 seed that makes among the embodiment, 30 ℃ of leavening temperatures, fermentation period 7d, other conditions are with embodiment 1.The output of A40926 reaches 218mg/L.
Embodiment 9
Fermention medium is formed: glucose 10.0g/L, and dextrin 30.0g/L, W-Gum 60.0g/L, yeast soak powder 10.0g/L, cold press soybean cake powder 20.0g/L, soy peptone 10.0g/L, Xie Ansuan 1.0g/L, NaCl 2.0g/L, pH to 8.0.
Be inoculated in the fermention medium with 10% (v/v) inoculum size by 1 seed that makes among the embodiment, 30 ℃ of leavening temperatures, fermentation period 7d, other conditions are with embodiment 1.The output of A40926 reaches 234mg/L.
Embodiment 10
Fermention medium is formed: glucose 10.0g/L, and dextrin 30.0g/L, W-Gum 60.0g/L, meat peptone 10.0g/L, yeast soak powder 10.0g/L, cold press soybean cake powder 20.0g/L, Xie Ansuan 1.0g/L, NaCl 2.0g/L, pH to 8.0.
Be inoculated in the fermention medium with 10% (v/v) inoculum size by 1 seed that makes among the embodiment, 30 ℃ of leavening temperatures, fermentation period 7d, other conditions are with embodiment 1.The output of A40926 reaches 256mg/L.
Embodiment 11
Fermention medium is formed: glucose 10.0g/L, dextrin 30.0g/L, W-Gum 60.0g/L, soy peptone 5.0g/L, meat peptone 10.0g/L, yeast soak powder 10.0g/L, cold press soybean cake powder 20.0g/L, Xie Ansuan 1.0g/L, NaCl 2.0g/L, pH to 8.0.
Be inoculated in the fermention medium with 10% (v/v) inoculum size by 1 seed that makes among the embodiment, 30 ℃ of leavening temperatures, fermentation period 7d, other conditions are with embodiment 1.The output of A40926 reaches 292mg/L.
Embodiment 12
Fermention medium is formed: glucose 10.0g/L, dextrin 30.0g/L, W-Gum 60.0g/L, soy peptone 5.0g/L, meat peptone 10.0g/L, yeast soak powder 5.0g/L, cold press soybean cake powder 20.0g/L, cottonseed meal 10.0g/L, Xie Ansuan 1.0g/L, NaCl 2.0g/L, pH to 8.0.
Be inoculated in the fermention medium with 10% (v/v) inoculum size by 1 seed that makes among the embodiment, 30 ℃ of leavening temperatures, fermentation period 7d, other conditions are with embodiment 1.The output of A40926 reaches 308mg/L.
Embodiment 13
Fermention medium is formed: glucose 10.0g/L, dextrin 30.0g/L, W-Gum 60.0g/L, soy peptone 5.0g/L, meat peptone 10.0g/L, yeast soak powder 5.0g/L, cold press soybean cake powder 10.0g/L, cottonseed meal 10.0g/L, Xie Ansuan 1.0g/L, NaCl 2.0g/L, pH to 8.0.
Be inoculated in the fermention medium with 10% (v/v) inoculum size by 1 seed that makes among the embodiment, 30 ℃ of leavening temperatures, fermentation period 7d, other conditions are with embodiment 1.The output of A40926 reaches 320mg/L.
Embodiment 14
Fermention medium is formed: glucose 10.0g/L, dextrin 30.0g/L, W-Gum 60.0g/L, soy peptone 5.0g/L, meat peptone 10.0g/L, yeast soak powder 5.0g/L, cold press soybean cake powder 10.0g/L, cottonseed meal 5.0g/L, Xie Ansuan 1.0g/L, NaCl 2.0g/L, pH to 8.0.
Be inoculated in the fermention medium with 10% (v/v) inoculum size by 1 seed that makes among the embodiment, 30 ℃ of leavening temperatures, fermentation period 7d, other conditions are with embodiment 1.The output of A40926 reaches 325mg/L.
Embodiment 15
Fermention medium is formed: glucose 10.0g/L, dextrin 30.0g/L, W-Gum 60.0g/L, soy peptone 5.0g/L, meat peptone 10.0g/L, yeast soak powder 5.0g/L, cold press soybean cake powder 10.0g/L, cottonseed meal 5.0g/L, Xie Ansuan 1.0g/L, NaCl 2.0g/L, CuSO
40.75ppm, pH to 8.0.
Be inoculated in the fermention medium with 10% (v/v) inoculum size by 1 seed that makes among the embodiment, 30 ℃ of leavening temperatures, fermentation period 7d, other conditions are with embodiment 1.The output of A40926 reaches 334mg/L.
Embodiment 16
Fermention medium is formed: glucose 10.0g/L, dextrin 30.0g/L, W-Gum 60.0g/L, soy peptone 5.0g/L, meat peptone 10.0g/L, yeast soak powder 5.0g/L, cold press soybean cake powder 10.0g/L, cottonseed meal 5.0g/L, Xie Ansuan 1.0g/L, NaCl 2.0g/L, CuSO
40.75ppm, pH to 7.0.
Be inoculated in the fermention medium with 10% (v/v) inoculum size by 1 seed that makes among the embodiment, 30 ℃ of leavening temperatures, fermentation period 7d, other conditions are with embodiment 1.The output of A40926 reaches 304mg/L.
Embodiment 17
Fermention medium is formed: glucose 10.0g/L, dextrin 30.0g/L, W-Gum 60.0g/L, soy peptone 5.0g/L, meat peptone 10.0g/L, yeast soak powder 5.0g/L, cold press soybean cake powder 10.0g/L, cottonseed meal 5.0g/L, Xie Ansuan 1.0g/L, NaCl 2.0g/L, CuSO
40.75ppm, pH to 8.0.
Be inoculated in the fermention medium with 10% (v/v) inoculum size by 1 seed that makes among the embodiment, 28 ℃ of leavening temperatures, fermentation period 7d, other conditions are with embodiment 1.The output of A40926 reaches 298mg/L.
Embodiment 18
Fermention medium is formed: glucose 10.0g/L, dextrin 30.0g/L, W-Gum 60.0g/L, soy peptone 5.0g/L, meat peptone 10.0g/L, yeast soak powder 5.0g/L, cold press soybean cake powder 10.0g/L, cottonseed meal 5.0g/L, Xie Ansuan 1.0g/L, NaCl 2.0g/L, CuSO
40.75ppm, pH to 8.0.
Be inoculated in the fermention medium with 10% (v/v) inoculum size by 1 seed that makes among the embodiment, 30 ℃ of leavening temperatures, fermentation period 5d, other conditions are with embodiment 1.The output of A40926 reaches 366mg/L.
Embodiment 19
Fermention medium is formed: glucose 10g/L, W-Gum 10g/L, cold press soybean cake powder 5g/L, meat peptone 2g/L, Xie Ansuan 3g/L, CuSO
40.5ppm, pH to 5.0.
Be inoculated in the fermention medium with 10% (v/v) inoculum size by 1 seed that makes among the embodiment, 20 ℃ of leavening temperatures, fermentation period 7d, other conditions are with embodiment 1.The output of A40926 reaches 234mg/L.
Embodiment 20
Fermention medium is formed: glucose 10g/L, Zulkovsky starch 20g/L, soy peptone 2g/L, Xie Ansuan 0.5g/L, CuSO
410ppm, pH to 8.5.
Be inoculated in the fermention medium with 10% (v/v) inoculum size by 1 seed that makes among the embodiment, 40 ℃ of leavening temperatures, fermentation period 7d, other conditions are with embodiment 1.The output of A40926 reaches 197mg/L.
Embodiment 21
Fermention medium is formed: dextrin 10g/L, and Zulkovsky starch 5g/L, cold press soybean cake powder 40g/L, Tryptones 2g/L, yeast soak powder 50g/L, Xie Ansuan 1g/L, NaCl 1g/L, pH to 7.0.
Be inoculated in the fermention medium with 10% (v/v) inoculum size by 1 seed that makes among the embodiment, 37 ℃ of leavening temperatures, fermentation period 7d, other conditions are with embodiment 1.The output of A40926 reaches 175mg/L.
Embodiment 22
Fermention medium is formed: glucose 5g/L, hot moulding soybean cake powder 5g/L, Tryptones 20g/L, Xie Ansuan 1g/L, NaCl 5g/L, pH to 7.0.
Be inoculated in the fermention medium with 10% (v/v) inoculum size by 1 seed that makes among the embodiment, 37 ℃ of leavening temperatures, fermentation period 7d, other conditions are with embodiment 1.The output of A40926 reaches 190mg/L.
Embodiment 23
Fermention medium is formed: glucose 20g/L, and dextrin 80g/L, W-Gum 60g/L, hot moulding soybean cake powder 40g/L, cottonseed meal 30g/L, soy peptone 20g/L, meat peptone 20g/L, yeast soak powder 100g/L, Xie Ansuan 1g/L, NaCl 2g/L, pH to 8.0.
Be inoculated in the fermention medium with 10% (v/v) inoculum size by 1 seed that makes among the embodiment, 30 ℃ of leavening temperatures, fermentation period 7d, other conditions are with embodiment 1.The output of A40926 reaches 289mg/L.
The comparative example 1
Press document " Zuzana TD; Fabrizio D; Salvatore M; et al.Design of mineralmedium for growth of Actinomadura sp.ATCC39727; producer of theglycopeptide A40926:effects of calcium ions and nitrogen sources[J] .ApplMicrobiol Biotechnol; 2004,65:671-677. " described method; will be inoculated in the 250ml fermentation shake flask that liquid amount is 20ml with inoculum size 10% (v/v) by 1 seed liquor that makes among the embodiment and ferment; 30 ℃ of temperature, fermentation period 5d.Fermentation ends secondary fermentation liquid is transferred pH to 12.0 with NaOH, centrifuging and taking supernatant behind 50 ℃ of incubation 1h, and HPLC measures, and the output of A40926 is 92mg/L.Wherein fermention medium is MM-103/Gln:L-Gln 2.0g/L, K
2HPO
40.5g/L, MgSO
40.2g/L, FeSO
40.01g/L, glucose 10.0g/L, pH7.0-7.2.
Claims (10)
1. fermention medium that is used for Ye Ye village actinomycetes (Nonomuraea.sp) fermentative production microbiotic A40926, comprise carbon source and nitrogenous source, it is characterized in that, described carbon source is an organic carbon source, content is 5-180g/L, described nitrogenous source is an organic nitrogen source, and content is 2-210g/L, and described content is by the cumulative volume of substratum.
2. fermention medium as claimed in claim 1, it is characterized in that, described organic carbon source is one or more in glucose, maltodextrin, W-Gum and the Zulkovsky starch, and described organic nitrogen source is one or more in soybean cake powder, cottonseed meal, peptone and the yeast extract/powder.
3. fermention medium as claimed in claim 1 is characterized in that, also further comprises in amino acid, metal ion, mineral substance and the defoamer one or more in the described fermention medium.
4. fermention medium as claimed in claim 3 is characterized in that, described amino acid is one or more in Xie Ansuan, leucine and the Isoleucine; Described metal ion is one or more in cupric ion, magnesium ion and the ferrous ion; Described mineral substance is NaCl.
5. fermention medium as claimed in claim 1 is characterized in that, described fermention medium comprises:
5-20g/L glucose;
At least a in 5-80g/L maltodextrin, W-Gum and the Zulkovsky starch;
At least a in 2-40g/L soybean cake powder, cottonseed meal and the peptone;
At least a in 5-100g/L yeast extract and the yeast extract powder; With
0.5-3.0g/L Xie Ansuan.
6. fermention medium as claimed in claim 1, it is characterized in that described fermention medium comprises: glucose 5-20g/L, dextrin 10-80g/L, W-Gum 10-60g/L, cold press soybean cake powder 5-40g/L, cottonseed meal 5-30g/L, soy peptone 2-20g/L, meat peptone 2-20g/L, yeast soak powder 5-100g/L, Xie Ansuan 0.5-3.0g/L, NaCl 1.0-5.0g/L and CuSO
40.5-10.0ppm.
7. the fermentation method for producing of a microbiotic A40926 is characterized in that, comprises step:
(a) seed liquor of Ye Ye village actinomycetes (Nonomuraea.sp) is inoculated in carries out liquid fermentation and culture in the fermention medium, described fermention medium is aforesaid each fermention medium;
(b) from fermented liquid, isolate microbiotic A40926.
8. method as claimed in claim 7 is characterized in that, in step (a), described Ye Ye village actinomycetes are Ye Ye village actinomycetes ATCC39727.
9. method as claimed in claim 7 is characterized in that, in step (a), the temperature of described fermentation culture is 20-40 ℃.
10. method as claimed in claim 7 is characterized in that, in step (a), the pH of described fermentation culture is 5.0-8.5.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201010164616.4A CN102234675B (en) | 2010-04-29 | 2010-04-29 | Fermentation medium and fermentation method of producing A40926 with Nonomuraea.sp by fermentation |
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| CN201010164616.4A CN102234675B (en) | 2010-04-29 | 2010-04-29 | Fermentation medium and fermentation method of producing A40926 with Nonomuraea.sp by fermentation |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN105671110A (en) * | 2015-05-05 | 2016-06-15 | 重庆乾泰生物医药有限公司 | Method of producing dalbavancin precursor A40926 |
| CN110105435A (en) * | 2019-05-08 | 2019-08-09 | 东莞东阳光药物研发有限公司 | A kind of fermentation medium and fermentation process producing A40926 |
| CN110551786A (en) * | 2019-09-12 | 2019-12-10 | 浙江海正药业股份有限公司 | Fermentation medium for increasing yield of A40926B 0 and method thereof |
| CN112625925A (en) * | 2021-01-08 | 2021-04-09 | 浙江大学 | High-yield strain of dalbavancin precursor A40926B0 and application thereof |
| CN113980860A (en) * | 2021-11-23 | 2022-01-28 | 天津商业大学 | Nonomuria of high-yield pentostatin and 2 '-amino-2' -deoxyadenosine and application thereof |
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| CN1732263A (en) * | 2002-10-23 | 2006-02-08 | 维柯龙药品公司 | Genes and proteins for the biosynthesis of the glycopeptide antibiotic A40926 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105671110A (en) * | 2015-05-05 | 2016-06-15 | 重庆乾泰生物医药有限公司 | Method of producing dalbavancin precursor A40926 |
| CN105671110B (en) * | 2015-05-05 | 2019-02-01 | 重庆乾泰生物医药有限公司 | A method of producing Dalbavancin precursor A40926 |
| CN110105435A (en) * | 2019-05-08 | 2019-08-09 | 东莞东阳光药物研发有限公司 | A kind of fermentation medium and fermentation process producing A40926 |
| CN110105435B (en) * | 2019-05-08 | 2023-12-08 | 宜昌东阳光生化制药有限公司 | Fermentation medium and fermentation method for producing A40926 |
| CN110551786A (en) * | 2019-09-12 | 2019-12-10 | 浙江海正药业股份有限公司 | Fermentation medium for increasing yield of A40926B 0 and method thereof |
| WO2021047431A1 (en) * | 2019-09-12 | 2021-03-18 | 浙江海正药业股份有限公司 | Fermentation culture medium and fermentation method capable of increasing yield of a40926 b0 |
| CN110551786B (en) * | 2019-09-12 | 2021-12-07 | 浙江海正药业股份有限公司 | Fermentation medium for increasing yield of A40926B 0 and method thereof |
| CN112625925A (en) * | 2021-01-08 | 2021-04-09 | 浙江大学 | High-yield strain of dalbavancin precursor A40926B0 and application thereof |
| CN112625925B (en) * | 2021-01-08 | 2022-04-19 | 浙江大学 | High-yield strain of dalbavancin precursor A40926B0 and application thereof |
| CN113980860A (en) * | 2021-11-23 | 2022-01-28 | 天津商业大学 | Nonomuria of high-yield pentostatin and 2 '-amino-2' -deoxyadenosine and application thereof |
| CN113980860B (en) * | 2021-11-23 | 2023-09-08 | 天津商业大学 | Nonomuria with high yield of prastatin and 2 '-amino-2' -deoxyadenosine and application thereof |
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